Prostaglandins are a group of hormone like substances which are known to play a significant factor in virtually all body function. In particular, prostaglandins play important roles in controlling the cardiovascular and immunological systems of the human body. Yet as important are prostaglandins for human health, their production is totally dependent on the dietary intake of a specialized group of fatty acids known as essential fatty acids. Essential fatty acids cannot be made by the human body, and must be supplied in the diet to provide sufficient precursors from which to synthesize prostaglandins. The primary essential fatty acids belong to the Omega 6 family of essential fatty acids. The complexity and dynamics of the transformation of these Omega 6 essential fatty acids into prostaglandins is shown in FIG. 1.
The complexity of Omega 6 essential fatty acid metabolism, and thus the determination of which prostaglandins are produced, is due to the activity of various enzymes responsible for the biological transformation of these essential fatty acids. Differences in the enzyme activity control the relative levels of the true prostaglandin precursors: dihomo gamma linolenic acid (DGLA) and arachidonic acid (AA). The prostaglandins of the one series derived from DGLA are beneficial for the cardiovascular system, stimulate the immune system, and control hormone synthesis and release. On the other hand, the prostaglandins of the two series derived from AA can inhibit cardiovascular function, depress the immune system, and generally have diameterically opposed physiological functions to prostaglandins of the one series. To maintain proper body function, both series one and two prostaglandins must be formed. Therefore, it is the balance of DGLA to AA in each body's cell that eventually determines the exact ratio of the one and two series prostaglandins that are formed. An overabundance of either the one or two series prostaglandins is not consistent with optimal physiological performance. The ratio of DGLA to AA is ultimately determined by the two primary enzymes that control the ratio of DGLA and AA in each cell. These two enzymes are delta-6 desaturase (D6D) and delta-5 desaturase (D5D).
The enzymes D6D and D5D are the rate controlling factors which determine the amounts of each of the prostaglandin precursors which will ultimately give rise to one series prostaglandins or two series prostaglandins. This becomes a primary factor for the treatment and possible prevention of cardiovascular disorders as the prostaglandins derived from AA (especially thromboxane A.sub.2) are considered to be the primary cause of cardiovascular disease.sup.1, whereas prostaglandins derived from DGLA (especially PGE.sub.1) are considered to be important in reducing the probability of developing cardiovascular disease..sup.2 Likewise, certain prostaglandins derived from AA (such as PGE.sub.2 and thromboxane A.sub.2) suppress the immune system, while prostaglandins from DGLA (such as PGE.sub.1) stimulate the immune system. Prostaglandins are also be formed from eicosapentaenoic acid (EPA). However, compared to the powerful physiological actions of prostaglandins of the one and two series, those derived from EPA are relatively neuter in theirphysiological actions.
Because EPA is a prevelant constituent in certain diets such as the Greenland Eskimos, and since the Greenland Eskimos have a very low incidence of cardiovascular disease, it has been assumed that EPA can treat or provide prophylaxis against various aspects of cardiovascular disease. This has been disclosed in British Patent Nos. 1,604,554 and 2,033,745.
Likewise, prior art has recognized the beneficial effects of GLA and/or DGLA as a treatment for cardiovascular disease in German Patent No. 2,749,492 and even earlier prior art concerning GLA in British Patent No. 1,082,624.
The use of a combination of many Omega 6 fatty acids with EPA and other Omega 3 fatty acids (i.e. docosahexanoic acid or DHA) which are not direct precursors for prostaglandin synthesis was disclosed in U.S. Pat. No. 4,526,902. However, this particular patent teaches that the roles of EPA and another fatty acid docsahexaenoic acid (DHA) are to compete with AA for various enzymes (i.e. cyclooxygenase) important in the production of prostaglandins, thereby leading to the inhibition of series two prostaglandins. This art does not refer to the critical role of EPA alone in its inhibitory action of the D5D enzyme. This prior art also makes the assertion that all Omega 6 fatty acids such as linoleic acid, GLA, and DGLA are biologically equivalent in terms of producing prostaglandins of the one series, and in particular PGE.sub.1.
It has been shown that in human adipose tissue (the primary storage site of fat) the ratio of linoleic acid to GLA to DGLA is approximately 100:2:1..sup.3 The reason for such a radically altered ratio of Omega 6 fatty acids is their increased biological potency beyond the enzymatic step catalyzed by the enzyme delta-6-desaturase in the conversion of linoleic acid into GLA (see FIG. 1). As an example, it has been estimated that GLA was 163 times more effective in lowering cholesterol levels in humans than an equivalent dose of linoleic acid..sup.4 Likewise, studies in primates have indicated that DGLA has twice the biological potency of GLA in terms of reducing platelet aggregation which is mediated by the formation of PGE.sub.1..sup.5 Furthermore, there is strong evidence that with increasing age the body's ability to produce GLA from linoleic acid is highly compromised therefore making the assertion of the equivalence of all Omega 6 fatty acids even more unlikely..sup.6,7 These results of biological potency corresponds well with the actual levels of Omega 6 fatty acids found in humans. What this means is that to assume that all Omega 6 fatty acids have the same biological potency in terms of prostaglandin production would be to grossly skew the balance of GLA and DGLA to EPA required to optimize prostaglandin levels of the one and two series prostaglandins.
U.S. Pat. No. 4,681,896 has taught that combinations of activated Omega 6 fatty acids with combinations of Omega 3 fatty acids are useful in the treatment of atopic disorders. Although this patent discloses "that the presence of n-3 fatty acids in a combination will lead to some inhibition of the conversion of DGLA to arachidonic acid by the delta-5-desaturase", the patent does not disclose that certain weight combinations of activated Omega 6 fatty acids and Omega 3 fatty acids (i.e. EPA) would be benefical, whereas other weight combinations are harmful to humans. Likewise, it is not taught in the general literature that certain weight combinations of activated Omega 6 essential fatty acids (such as GLA or DGLA) in combination with EPA would be beneficial, whereas other weight combinations would be detrimental.
The reason why prior art has not discovered this critical aspect of essential fatty metabolism is that no long term human studies have been conducted with combinations of activated Omega 6 essential fatty acids and EPA. This is important since the conversion of DGLA to AA in humans is relatively slow, yet proceeds continuously..sup.8 This slow conversion of DGLA into AA can be exceptionally harmful. The studies described in this patent illustrates deficiencies in the prior art.